The present invention relates broadly to the measuring field of minute temperature differences.
Thermographic investigations and tests are usually carried out by means of infrared microscopes, for particularly measuring microtemperature differences at a resolution of 0.1.degree. C. and at a spatial resolution of about 15 micrometers.
Small, local temperature differences are to be ascertained, for example, in the field called microbiology, particularly for purposes of medical research or diagnostics. In particular, it is desirable to ascertain metabolic processes in living cells, if these processes are accompanied by temperature changes. Conducting tests on living cells has many advantages over procedures, such as dyeing, which lead to the death of the cells. Thermographic investigations are of particular interest, for example, for diagnosing cancer because it is known that cells suspected of concerous abnormalities exhibit a different metobolism as compared with normal cells and these differences reflect differences in the accompanying temperature changes.
The total energy being converted in metabolic processes of an organism can be divided into a resting energy conversion and energy conversion due to motion. Both energy quantities are extracted from the cells by means of biochemical reactors. Part of the energy is used for the generation of new cells and their components, another portion is transmitted to the immediate environment. Thermographic investigations must lead to the detection of that local heat transfer into the environment.
It can readily be seen that detection of local temperature differences in an organism depends critically upon maintaining the temperature of that organism constant as far as creating a suitable environment for the measurement of local temperature differences is concerned. The thermographic or thermometric investigation is to be carried out by means of a conventional microscope under utilization of still- or motion picture or TV cameras. The invention is specifically concerned with these measurements as well as high the generation of an adequately stabile, thermal environment for such measurements.
It is an object of the present invention to improve the thermometric or thermographic measurement of minute local temperature differences in an object. It is a further object of the present invention to improve such measurements by specifically stabilizing the thermal environment for such an object.
It is another object of the present invention to improve microscopes used for measuring minute temperature differences.
It is a somewhat broader object of the present invention to improve the environment of, for, and in such microscopes as far as the temperature and its control of the object under investigation is concerned.
It is a specific object of the present invention to improve such microscopes being provided, e.g., with an object carrier table that is heatable.
It is another specific object of the present invention to improve microbiological investigations.
In accordance with the preferred embodiment of the present invention, it is suggested to use an object carrier for such thermographic or thermometric investigations which includes an embedded layer of a liquid crystal material, whereby the object-carrying cover for that material is to be very thin, preferably in the order of a few micrometers for assuring good thermal and heat-conductive contact between the crystal layer and the object. The invention makes use of the known fact that liquid crystals with a helical molecular structure exhibit a temperature-selective reflection which is highly localized at a resolution of below 10.sup.-2 centigrades at a spatial resolution of about 200 Angstroms, and a temporal resolution of about 33 cycles per second. Such an object carrier is, indeed, well suited for detecting local temperature differences.
As far as the environmental thermal stabilization is concerned, it is suggested that this carrier be provided with a light-absorbing bottom, to be exposed to a controllable source of radiation. The total reflection of the carrier as established primarily by the liquid crystal layer is ascertained to, thereby, measure its average temperature (including the temperature of the object), and to control the above-mentioned light source (e.g., through a diaphragm or the like) to, thereby, stabilize the average temperature. Temperature stabilization in the order of 10.sup.-3 centigrades or better can be achieved in this manner.
It can, thus, be seen that the novel carrier performs two functions. First of all, it operates as the temperature detector for the object under investigation. The liquid crystal responds locally to local, thermal differences by changing its reflectivity to, thereby, indicate temperature changes in the adjacent object (e.g., a cell or microorganism). In addition, it keeps its average temperature constant to, thereby, stabilize the thermal environment for the object it carries so that, e.g., local cell activity can, indeed, be traced by the variation in temperature on account of that activity and for no other reason.
It was found that unter utilization of an otherwise regular thermometric microscope, temperature differences of less than 10.sup.-2 centigrades at distances smaller than one micrometer can be detected. The accuracy depends to some extent upon the liquid crystal material; cholesteric liquid crystals are highly satisfactory. This is an improvement by more than one order of magnitude. Also, short-term temperature variations can be detected better than before.